Ethanol → Ethyl (S)-[[1-(2-[[(1-amino-6-isoquinolinyl)carbonyl]amino]-1-oxopropyl)piperidin-4-yl]oxy]acetic acid hydrochloride

HRID 1279027Notes

Reaction equation

HRID 1279027 reaction equation
[ClH:1].[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([NH:15][C@@H:16]([CH3:30])[C:17]([N:19]3[CH2:24][CH2:23][CH:22]([O:25][CH2:26][C:27]([OH:29])=[O:28])[CH2:21][CH2:20]3)=[O:18])=[O:14])=[CH:10][CH:11]=2)[CH:6]=[CH:5][N:4]=1.S(=O)(=O)(O)O.[OH-].[Na+].C(=O)([O-])O.[Na+].[CH2:43](O)[CH3:44]>[Cl-].[Na+].O.ClCCl>[ClH:1].[CH2:43]([C@H:26]([O:25][CH:22]1[CH2:21][CH2:20][N:19]([C:17](=[O:18])[CH:16]([NH:15][C:13]([C:9]2[CH:8]=[C:7]3[C:12](=[CH:11][CH:10]=2)[C:3]([NH2:2])=[N:4][CH:5]=[CH:6]3)=[O:14])[CH3:30])[CH2:24][CH2:23]1)[C:27]([OH:29])=[O:28])[CH3:44]

Participants

8

Reactant 5

HCID 702EthanolHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 69780722(S)-[[1-(2-[[(1-amino-6-isoquinolinyl)carbonyl]amino]-1-oxopropyl)piperidin-4-yl]oxy]acetic acid hydrochloride

Product 1

HCID 86758500Ethyl (S)-[[1-(2-[[(1-amino-6-isoquinolinyl)carbonyl]amino]-1-oxopropyl)piperidin-4-yl]oxy]acetic acid hydrochloride

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of 394 mg of (S)-[[1-(2-[[(1-amino-6-isoquinolinyl)carbonyl]amino]-1-oxopropyl)piperidin-4-yl]oxy]acetic acid hydrochloride in 10 mL of ethanol at 0° C. was added 0.55 mL of sulfuric acid (95-98%). The reaction mixture was allowed to warm to room temperature and after 2 hours 5 mL of 2N aqueous sodium hydroxide, 20 mL of brine, 20 mL of 5% aqueous sodium hydrogencarbonate and 40 mL of dichloromethane was added. The organic layer was separated and the aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried (sodium sulfate) and concentrated. Purification using column chromatography (silica gel, dichloromethane:ethanol =9:1) and lyophilisation (t-butanol/hydrochloric acid) yielded 265 mg of the title compound.

Workup

  1. additionwas added
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted three times with dichloromethane
  4. dry with materialThe combined organic layers were dried (sodium sulfate)
  5. concentrationconcentrated
  6. customPurification

Sources & evidence

ORD record
ord-2f2e6c15f92d46958dbdbc88bea329bd
Source dataset
uspto-grants-2002_09
Patent number
US06444672B1

Reaction notes

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